Adrenal Dysfunction/ Adrenal Medulla Flashcards
Primary Adrenocortical Insufficiency (Addison Disease) is characterized by what
defect within adrenal gland
Primary Adrenocortical Insufficiency (Addison Disease) is cased by what
destruction of gland by tuberculosis, metastatic tumor
an autoimmune disorder
inborn errors of steroid hormone synthesis
Clinical Features of Primary Adrenocortical Insufficiency (Addison Disease) are
aldosterone deficiency
cortisol deficiency
androgen deficiency
consequences of aldosterone deficiency are
decreased renal absorption of Na+ (hyponatremia and polyuria)
extracellular fluid depletion (reduced plasma volume, hypotension, dehydration)
hyperkalemia
consequences of cortisol deficiency
inability to handle stress hypoglycemia when stressed or fasting weakness and fatigue hypotension decreased appetite and weight loss anemia hyperpigmentation GI discomfort, nausea and occasional vomiting
consequences of androgen deficiency
loss of pub and axillary hair in females
Secondary Adrenocortical Insufficiency is associated with what
insufficient production of ACTH
insufficient production of renin
clinical supraphysiological doses of synthetic glucocorticoids cause what (and how)
Secondary Adrenocortical Insufficiency associated with ACTH
surpasses the hypothalamic-pituitary axis and depression of ACTH leads to adrenal atrophy
pseudohypoaldosteronism is cased by what
loss of function mutant in the mineralocorticoid receptor
pseudohypoaldosteronism is characterized by what
severe salt wasting in neonate
hyperkalemia
metabolic acidosis
failure to respond to treatment with mineralocorticoids
cushing syndrome is characterized by what
excessive cortisol secretion
major causes of cushing syndrome are?
injection of pharmacological doses of glucocorticoids
excessive secretion of ACTH by pituitary (Cushing’s Disease)
ectopic, non-endocrine, ACTH secreting tumors
tumors of adrenal cortex
patients with cushing syndrome have what clinical facial feature
moon face with acne
clinical features of cushing syndrome are?
obesity hypertension glucose intolerance hirsutism amenorrhea purple cutaneous striae bruise easy osteoporosis acne poor wound healing mental effects
what are the mental effects related to cushings
personality changes
insomnia
depression
poor wound healing seen in bushings is due to the inhibitor effects of cortisol on what
production of mediators of inflammation production of chemotaxic and mitogenic mediators fibroblast proliferation collagen biosynthesis circulating levels of WBCs
Primary aldosteronism (Conn Syndrome) is caused by what?
autonomous secretion of aldosterone, usually by ademona arising from zona glomerulosa
Primary aldosteronism (Conn Syndrome) symtoms are
mild hypertension
hypokalemia
metabolic alkalosis
low plasma renin
in patients with conn syndrome plasma renin levels are what?
depressed (as a result of expanded extracellular volume)
secondary aldosteronism is cased by what
inappropriate activation of renin-angiotensin system
Congenital Adrenal Hyperplasia (CAH) refers to what
group of genetically transmitted enzymatic deficiencies in the biosynthesis pathway for adrenal steroids
hyperplasia results when?
deficiency in biosynthetic pathway for cortisol
deficiency in biosynthetic pathway for cortisol result in what
decrease in negative feedback inhibition resulting in rise in ACTH secretion
what actually induces the hyperplasia of the adrenal gland
tropic effect of ACTH
in hyperplasia there is a build up of what
steroid intermediates directly behind the enzymatic block
most frequent block in congenital adrenal hyperplasia is in what
21-hydroxylase enzyme
21-hydroxylase enzyme block is characterized by what
virilizing syndrome due to excess androgen production in the adrenal and non-adrenal tissues from pre block intermediates
in females 21-hydroxylase enzyme block leads to what
fusion of labia and clitoral hypertrophy if exposure to androgens occurs before 12 weeks
exposure after 12 weeks leads to clitoral hypertrophy alone
in males 21-hydroxylase enzyme block leads to what
increase in somatic growth
premature closure of epiphyseal plate
early maturation of genitalia
development of secondary sexual characteristics
adrenal medulla contains what type of cells
modified postganglionic cells (chromaffin cells)
chromaffin cells secrete what and into what
catecholamines directly into the blood stream
chromaffin cells are innervated by what fibers
cholinergic preganglionic fibers
what are the principle catecholamates released from the adrenal medulla
epinephrine and norepinephrine
aprox 80% of chromaffin cells secrete what
epinephrine
the only source of circulating epinephrine is where
adrenal gland
most norepinephrine in the blood is released from where
nerve terminals
chatecholamine release by adrenal medulla is an important part in acute response to what?
stress
catecholamine biosynthesis involves the stepwise modification of what to what
tyrosine to dopamine
the first step of converting tyrosine to dopamine is what
tyrosine to dihydroxyphenylalanine (DOPA) by tyrosine hydroxylase
what is the rate limiting step in the conversion of tyrosine to dopamine
tyrosine to dihydroxyphenylalanine (DOPA) by tyrosine hydroxylase
what is the transporter that brings dopamine into the chromaffin granule
VMAT
in the chromaffin granule what happens to dopamine
converted to norepinephrine
what happens to norepinephrine in cromaffin granule
exits granule via facilitated diffusion converted to epinephrine in cytoplams
norepi becomes epi how
phenylthanolamine-N-methyltransferase (PNMT)
what happens to epinephrine created in cytoplasm of chromaffin cells
transported back into chromaffin granule via VMAT where it is stored until release
catecholamines are stored in chromaffin granules in a complex with what
ATP, Ca2+, and chromogranin
about 50% of circulating catecholamine pool is loosely bound to what?
albumin
the adrenal medulla is usually activated in concert with what
rest of sympathetic nervous system
what is released from preganglionic fibers to promote the release of catecholamines that are stored in chromaffin granules
acetylcholine
acetyl choline promotes transcription of what enzyme
tyrosine hydroxylase
what connects adrenal medulla and cortex
portal system
cortisol promotes what (in terms of catecholamines)
promotes conversion of norepinephrine to epinephrine
induces phenylethanolamine-N-methyltransferase (PNMT)
cortisol prevents chromaffin cells from what?
developing into postganglionic neurons
catecholamine-degrading enzymes (name them
monoamine oxidase (MAO) catecholamine-o-methyltransferase (COMT)
what happens to NE released by nerve terminals
either repackaged into secretory granules or degraded by MAO and COMT
tissues degrade catecholamines predominantly how?
COMT-mediated methylation
major classes of metabolites resulting from the inactivation of catecholamines (name them)
metanephrines
vanillylmandelic acid
useful measure of total catecholamine production
urinary levels of metanephrines and vanillylmandelic acid
adrenal medulla releases catecholamines into the blood in response to what
sympathetic activation caused by fright, danger, trauma, hemorrhage, hypoglycemia, vigorous exercise
alpha 1 adrenergic receptors work via what pathway
Gd: IP3, Ca2+, DAG
alpha 2 adrenergic receptors work via what pathway
Gi: decreasing cAMP
then beta adrenergic receptors work via what pathway
Gs: cAMP
Pheochromocytomas (what are they)
catecholamine-producing tumors of chromaffin cells of the adrenal medulla or extra-adrenal ganglia
Pheochromocytomas (clinical features)
hypertension, tachycardia, tremors, sweating, anxiety, headache
